Biology subjects

Bener, M. B.

Publications and source records attributed to Bener, M. B..

5 recordsLinked to original sources

bioRxiv2025

Detection of dedifferentiated stem cells in Drosophila testis

Tissue homeostasis relies on the stable maintenance of the stem cell pool throughout an organisms lifespan. Dedifferentiation, a process in which partially or terminally differentiated cells revert to a stem cell state, has been observed in a wide range of stem cell systems, and it has been implicated in the mechanisms for stem cell maintenance. Dedifferentiated stem cells are morphologically indistinguishable from original stem cells, making them challenging to identify. Therefore, whether dedifferentiated stem cells have any distinguishable characteristics compared with original stem cells is poorly understood. The Drosophila testis provides a well-established model to study dedifferentiation. While our previous live imaging analyses have identified dedifferentiation events constantly occurring at steady state, existing genetic marking methods fail to detect most of the dedifferentiated stem cells and thus significantly underestimate the frequency of dedifferentiation events. Here, we established a genetic tool with improved sensitivity and used live imaging and mathematical modeling to evaluate the system. Our findings indicate that the specificity of lineage-specific promoters is critical for successfully identifying dedifferentiated stem cells.

developmental biology↗

bioRxiv2024

Asymmetric stem cell division maintains the genetic heterogeneity of tissue cells

Within a given tissue, the stem cell niche provides the microenvironment for stem cells suitable for their self-renewal. Conceptually, the niche space constrains the size of a stem-cell pool, as the cells sharing the niche compete for its space. It has been suggested that either neutral-or non-neutral-competition of stem cells changes the clone dynamics of stem cells. Theoretically, if the rate of asymmetric division is high, the stem cell competition is limited, thus suppressing clonal expansion. However, the effects of asymmetric division on clone dynamics have never been experimentally tested. Here, using the Drosophila germline stem cell (GSC) system, as a simple model of the in-vivo niche, we examine the effect of division modes (asymmetric or symmetric) on clonal dynamics by combining experimental approaches with mathematical modeling. Our results suggest that the rate of asymmetric division positively correlates with the time a stem cell clone takes to expand. Taken together, our data suggests that asymmetric division is essential for maintaining the genetic variation of stem cells and thus serves as a critical mechanism for safeguarding fertility over the animal age or preventing multiple disorders caused by the clonal expansion of stem cells.

developmental biology↗

bioRxiv2023

Dedifferentiating germ cells regain stem-cell specific polarity checkpoint prior to niche reentry

In the Drosophila germline stem cell system, maintenance of the stem cell pool requires "dedifferentiation", in which differentiating cells reattach to the niche and reacquire stem cell properties. However, the mechanism of dedifferentiation remains poorly understood. Here, using long-term live imaging, we show that dedifferentiated cells immediately re-enter mitosis with correct spindle orientation after reattachment to the niche. Analysis of cell cycle markers revealed that these dedifferentiating cells are all in G2 phase. In addition, we found that the observed G2 block during dedifferentiation likely corresponds to a centrosome orientation checkpoint (COC), a previously reported polarity checkpoint. We show that re-activation of a COC is likely required for the dedifferentiation thus ensuring asymmetric division even in dedifferentiated stem cells. Taken together, our study demonstrates the remarkable ability of dedifferentiating cells to reacquire the ability to divide asymmetrically.

developmental biology↗

bioRxiv2021

Acetylated microtubules are required for maintenance of the barrier between two adjacent tissues

Microtubule acetylation is found in populations of stable, long-lived microtubules, occurring on the conserved lysine 40 (K40) residue of -tubulin, catalyzed by -tubulin acetyltransferases (TATs). K40 acetylation has been shown to stabilize microtubules via enhancing microtubule resilience against mechanical stress. Here we show that Drosophila CG17003/leaky (Lky), an TAT, is required for proper oogenesis. We found that loss of lky disrupted the cell junction between germline cyst and follicle epithelial cells, adjacent cells that form an egg chamber. This resulted in leakage of germline contents into somatic follicle cells. The follicle cells that received germline-derived nanos gene product failed to maintain their cell fate, leading to an egg chamber fusion. The same phenotype was observed upon replacement of major -tubulin84BK40 with -tubulin84BK40A (non-acetylable tubulin), suggesting -tubulinK40 acetylation is required for the boundary integrity of these two adjacent tissues. Taken together, this study provides the first in vivo function of tubulin acetylation in maintaining the integrity of a tissue barrier.

developmental biology↗

bioRxiv2019

Mad dephosphorylation at the nuclear envelope is essential for asymmetric stem cell division

Stem cell niche signals act over a short range so that only stem cells but not the differentiating daughter cells receive the self-renewal signals. Drosophila female germline stem cells (GSCs) are maintained by short range BMP signaling; BMP ligands Dpp/Gbb activate receptor Tkv to phosphorylate Mad (phosphor-Mad or pMad) which accumulates in the GSC nucleus and activates the stem cell transcription program. pMad is highly concentrated in the nucleus of the GSC, but is immediately downregulated in the nucleus of the pre-cystoblast (preCB), a differentiating daughter cell, that is displaced away from the niche. Here we show that this asymmetry in the intensity of pMad is formed even before the completion of cytokinesis. A delay in establishing the pMad asymmetry leads to germline tumors through conversion of differentiating cells into a stem cell-like state. We show that a Mad phosphatase Dullard (Dd) interacts with Mad at the nuclear pore, where it may dephosphorylate Mad. A mathematical model explains how an asymmetry can be established in a common cytoplasm. It also demonstrates that the ratio of pMad concentrations in GSC/preCB is highly sensitive to Mad dephosphorylation rate. Our study reveals a previously unappreciated mechanism for breaking symmetry between daughter cells during asymmetric stem cell division.

developmental biology↗